RESUMO

Monte Carlo (MC)-based simulation is the most precise method in scatter correction for Cone-beam CT (CBCT). Nonetheless, the existing MC methods cannot be fully applied in clinical due to its low efficiency. The traditional MC simulations perform calculations via a particle-by-particle scheme, which leads to high computation costs because abundant photons do not reach the X-ray detector in transport. The conventional approaches cannot control where the particle ends. Hence, it unavoidably waste lots of time in transporting numerous photons that have no contribution to the signal at the detector, yielding a low computational efficiency. To solve the problem, an innovative GPU-based Metropolis MC (gMMC) method was proposed. Compared with the traditional ones, the Metropolis based algorithm utilizes a path-by-path sampling method. The method can automatically control each particle path and eventually accelerate the convergence. In this paper, we firstly take planning CT image as prior information because of its precise CT value, and utilize gMMC to estimate scatter signal. Then the scatter signals are removed from the raw CBCT projections. Afterwards, FDK reconstruction is performed to obtain the corrected image,some accelerating strategies including reducing photon history number, pixels sampling, projection angles sampling and reconstructed image down-sampling achieve adaptive fast CBCT image reconstruction. For having high computational efficiency, we implemented the whole workflow on a 4-GPU workstation. In order to verify the feasibility of the the method, the experiment of several cases are conducted including simulation, phantom, and real patient cases. Results indicate that the image contrast becomes better, the scatter artifacts are eliminated. The maximum error (emax), the minimum error (emin), the 95th percentile error (e95%), average error (¯e) are reduced from 264, 56, 14 and 21 HU to 28, 10, 3 and 7 HU in full-fan case, and from 387, 5, 19 and 95 HU to 39, 2, 2 and 6 HU in the half-fan case. In terms of computation time, the MC simulation time of all cases is within 2.5 seconds, and the total time is within 15 seconds.

RESUMO

BACKGROUND: The importance of the lipid-related biomarkers has been implicated in the pathological process and prognosis of acute myocardial infarction (AMI). Our work was conducted to discuss and compare the predictive ability of the neutrophil to high-density lipoprotein cholesterol (HDL-C) ratio (NHR) with other existing prognostic indices, for instance, the monocyte to HDL-C ratio (MHR) and the low-density lipoprotein cholesterol (LDL-C) to HDL-C ratio (LDL-C/HDL-C) in elderly patients with AMI. METHODS: Our population was 528 consecutive elderly AMI patients (65-85 years) who were enrolled from Tongji Hospital and grouped according to the cutoff points which were depicted by the receiver operating characteristic (ROC). The Kaplan-Meier curves were plotted with the survival data from the follow-up to investigate the difference between cutoff point-determined groups. Moreover, we assessed the impact of NHR, MHR, LDL-C/HDL-C on the long-term mortality and recurrent myocardial infarction (RMI) with Cox proportional hazard models. RESULTS: Mean duration of follow-up was 673.85 ± 14.32 days (median 679.50 days). According to ROC curve analysis, NHR ≥ 5.74, MHR ≥ 0.67, LDL-C/HDL-C ≥ 3.57 were regarded as high-risk groups. Kaplan-Meier analysis resulted that the high-NHR, high-MHR and high-LDL-C/HDL-C groups presented higher mortality and RMI rate than the corresponding low-risk groups in predicting the long-term clinical outcomes (log-rank test: all P < 0.050). In multivariate analysis, compared with MHR and LDL-C/HDL-C, only NHR was still recognized as a latent predictor for long-term mortality (harzard ratio [HR]: 1.96, 95% confidence interval [CI]: 1.02 to 3.75, P = 0.044) and long-term RMI (HR: 2.23, 95% CI: 1.04 to 4.79, P = 0.040). Furthermore, the positive correlation between NHR and Gensini score (r = 0.15, P < 0.001) indicated that NHR was relevant to the severity of coronary artery to some extent. CONCLUSIONS: NHR, a novel laboratory marker, might be a predictor of the long-term clinical outcomes of elderly patients with AMI, which was superior to MHR and LDL-C/HDL-C.

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Two new species of Rhabdocoela, namely Alcha sinensis n. sp. (Polycystididae) and Trigonostomum sinensis n. sp. (Trigonostomidae), were discovered from the intertidal zone of eastern Shenzhen City, China. For A. sinensis n. sp., the stylet consists of two symmetrical triangular plates and one lamellar plate. All three plates are jagged at their posterior ends. The anterior end of the stylet connects to a thick muscular layer, which causes its movement. For T. sinensis n. sp., the copulatory organ consists of a long-tubular stylet and two "T"-shaped plates (plate I and plate II). The stylet bends 120° at 25% of its length from the base and extends straight distally. Two "T" plates are connected to each other and surround the stylet. Plate I is hook-shaped at its distal end, and plate II has a similar length but only half the width of plate I. The phylogenetic (18S rDNA and 28S rDNA) results also support the establishment of these two new species. On the basis of the molecular phylogeny and morphology of the copulatory organ and bursa appendage, we propose a new categorization of the species of Trigonostomum.

RESUMO

Two new species of the genus Pogaina Marcus, 1954 (Provorticidae), namely Pogaina sinensis n. sp. and Pogaina shenzhenensis n. sp. are described from brackish water in the intertidal zone of Shenzhen Bay. For P. sinensis n. sp., the tubular stylet is slightly curved at the distal end and a fusiform structure with a flange is present at 66% of the stylet. The flange encircles the stylet, with its ends attached to the midpoint and the distal end of the stylet. For P. shenzhenensis n. sp., the stylet has a N-shaped overall morphology. A band provided with dense needle-like structures is present at the distal end of the stylet. Both the morphological (stylet) and phylogenetic (18S rDNA and 28S rDNA) analyses support the establishment of these two new species.

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BACKGROUND: Contrast-induced nephropathy (CIN) is acute renal failure observed after administration of iodinated contrast media during angiographic or other medical procedures. In recent years, many studies have focused on biomarkers that recognize CIN and/or predict its development in advance. One of the many biomarkers studied is the platelet-to-lymphocyte ratio (PLR). We performed a systematic review and meta-analysis to evaluate the correlation between PLR level and CIN. METHODS: Relevant studies were searched in PUBMED, EMBASE, and Web of Science until September 15, 2018. Case-control studies reporting admission PLR levels in CIN and non-CIN group in patients with acute coronary syndrome (ACS) were included. The pooled weighted mean difference (WMD) and 95% confidence intervals (95%CI) were calculated to assess the association between PLR level and CIN using a random-effect model. RESULTS: Six relevant studies involving a total of 10452 ACS patients (9720 non-CIN controls and 732 CIN patients) met our inclusion criteria. A meta-analysis of 6 case-control studies showed that PLR levels were significantly higher in CIN group than those in non-CIN group (WMDâ=â33.343, 95%CIâ=â18.863 to 47.823, P < .001, Iâ=â88.0%). CONCLUSION: For patients with ACS after contrast administration, our meta-analysis shows that on-admission PLR levels in CIN group are significantly higher than those of non-CIN group. However, large and matched cohort studies are needed to validate these findings and assess whether there is a real connection or just an association.

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Three-dimensional genome structure plays a pivotal role in gene regulation and cellular function. Single-cell analysis of genome architecture has been achieved using imaging and chromatin conformation capture methods such as Hi-C. To study variation in chromosome structure between different cell types, computational approaches are needed that can utilize sparse and heterogeneous single-cell Hi-C data. However, few methods exist that are able to accurately and efficiently cluster such data into constituent cell types. Here, we describe scHiCluster, a single-cell clustering algorithm for Hi-C contact matrices that is based on imputations using linear convolution and random walk. Using both simulated and real single-cell Hi-C data as benchmarks, scHiCluster significantly improves clustering accuracy when applied to low coverage datasets compared with existing methods. After imputation by scHiCluster, topologically associating domain (TAD)-like structures (TLSs) can be identified within single cells, and their consensus boundaries were enriched at the TAD boundaries observed in bulk cell Hi-C samples. In summary, scHiCluster facilitates visualization and comparison of single-cell 3D genomes.

RESUMO

BACKGROUND: Fetuin-A is an anti-inflammation and anti-calcification factor involved in the course of coronary artery disease (CAD). But the association between serum fetuin-A level and the prognosis of CAD patients was still controversial. To clarify the association between serum fetuin-A level and the prognosis of CAD patients, we conducted the present meta-analysis. METHODS: The included studies should be potentially relevant prospective studies published in English language before January 2019. The target population of the present meta-analysis was restricted to patients with CAD. The results of studies must report hazard ratio (HR) or Kaplan-Meier survival curve for all-cause mortality or incidence of secondary cardiovascular disease (CVD) events. The pooled HRs were analysed by the method of meta-analysis. RESULTS: A total of four prospective studies, including 4256 participants with CAD disease, were chosen to be included. The pooled HR for all-cause mortality was 0.57 (95% CI: 0.37-0.87), showing a statistically significant association between high serum fetuin-A level and low all-cause mortality in CAD patients. For the incidence of secondary CVD events, the pooled HR was 0.86 (95% CI: 0.60-1.23), indicating no statistically significant association between serum fetuin-A level and incidence of secondary CVD events in CAD patients. CONCLUSION: High serum fetuin-A level associated with lower all-cause mortality in patients with CAD. No association between serum fetuin-A level and incidence of secondary CVD events was found in patients with CAD.

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Monte Carlo (MC) method is commonly considered as the most accurate approach for particle transport simulation because of its capability to precisely model physics interactions and simulation geometry. Conventionally, MC simulation is performed in a particle-by-particle fashion. In certain problems such as computing scattered X-ray photon signal at a detector of CT, the conventional simulation scheme suffers from low efficiency mainly due to the fact that abundant photons are simulated but do not reach the detector. The computational resources spent on those photons are therefore wasted. To solve this problem, this study develops a novel GPU-based Metropolis MC (gMMC) with a novel path-by-path simulation scheme and demonstrates its effectiveness in an example problem of scattered X-ray photon calculation in CT. In contrast to the conventional MC approach, gMMC samples an entire photon path extending from the X-ray source to the detector using Metropolis-Hasting algorithm. The path-by-path simulation scheme ensures contribution of every sampled event to the signal of interest, improving overall efficiency. We benchmark gMMC against an in-house developed GPU-based MC tool, gMCDRR, which performs simulations in the conventional particle-by-particle fashion. gMMC reaches speed up factors of 37~48 times in simple phantom cases and 20-34 times in real patient cases. The results calculated by gMCDRR and gMMC agree well with average differences < 3%.

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A series of 8- and 11-substituted hybrids of oxoisoaporphine-tetrahydroisoquinoline have been designed and synthesized. The new derivatives strongly suppressed NO and iNOS production and modulated the production of cytokines by decreasing TNF-α and IL-1ß formation in lipopolysaccharide-activated BV-2 microglia and RAW 264.7 macrophages. Meanwhile, incubation of these derivatives with SH-SY5Y cells that were transfected with human APP containing the Swedish mutations significantly decreased the secretion of Aß42. Moreover, these hybrids could strongly inhibit the activity of acetylcholinesterase and butyrylcholinesterase. Further investigations in vivo indicated that the 8-substituted hybrid 3b significantly delayed paralysis caused by Aß1-42 toxicity in GMC101. In sum, these new hybrids could target multiple pathogenetic factors in Alzheimer's disease and merit further investigation.

RESUMO

The importance of tacrolimus in the treatment of myasthenia gravis (MG) as a substitute for corticosteroid-dependent immunosuppressive therapy is increasing. Thus far, however, no population pharmacokinetic (PopPK) analysis of tacrolimus in treating MG patients has been published. This article aimed to construct a PopPK model of tacrolimus for Chinese MG patients with the goal of improving its performance in MG treatment. A total of 253 trough concentration records were obtained from 83 Chinese MG patients. The effects of demographics, lifestyle and health status, biochemical test data, disease progression and treatment-related information (including co-administered medications) as covariates on the various parameters were investigated. The covariate selection was based on biological plausibility, clinical significance, statistical significance and reduction in inter-individual variability (IIV). Bootstrap and normalized prediction distribution error (NPDE) analysis were performed to validate the final model. A one-compartment PopPK model with first-order elimination and a fixed absorption phase was constructed. The estimated apparent oral clearance (CL/F) and apparent oral volume of distribution (V/F) were 3.6 L/h and 1700 L, respectively, in the MG patients. Hematocrit and blood urea nitrogen were identified as two covariates that significantly influenced the CL/F. Immunoglobulin treatment (PRO) also had the potential to influence V/F, which was consistent with the clinical observations and the high protein-binding property of tacrolimus. Other covariates including age, weight, gender and co-administered medications had no obvious influence on CL/F or V/F. The first PopPK model of tacrolimus in MG patients was established. The identified covariates were of biological plausibility and clinical importance to help individualize the dosing schedule in MG patients.

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Growth Differentiation Factor 8 (GDF8), also called myostatin, is a member of the transforming growth factor (TGF)-ß super-family. As a negative regulator of skeletal muscle growth, GDF8 is also associated with bone metabolism. However, the function of GDF8 in bone metabolism is not fully understood. Our study aimed to investigate the role of GDF8 in bone metabolism, both in vitro and in vivo. Our results showed that GDF8 had a negative regulatory effect on primary mouse osteoblasts, and promoted receptor activator of nuclear factor κB ligand (RANKL)-induced osteoclastogenesis in vitro. Intraperitoneal injection of recombinant GDF8 repressed bone formation and accelerated bone resorption in mice. Furthermore, treatment of aged mice with a GDF8 neutralizing antibody stimulated new bone formation and prevented bone resorption. Thus, our study showed that GDF8 plays a significant regulatory role in bone formation and bone resorption, thus providing a potential therapeutic pathway for osteoporosis.

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Hydrogen production via electrochemical water splitting is a promising approach for storing solar energy. For this technology to be economically competitive, it is critical to develop water splitting systems with high solar-to-hydrogen (STH) efficiencies. Here we report a photovoltaic-electrolysis system with the highest STH efficiency for any water splitting technology to date, to the best of our knowledge. Our system consists of two polymer electrolyte membrane electrolysers in series with one InGaP/GaAs/GaInNAsSb triple-junction solar cell, which produces a large-enough voltage to drive both electrolysers with no additional energy input. The solar concentration is adjusted such that the maximum power point of the photovoltaic is well matched to the operating capacity of the electrolysers to optimize the system efficiency. The system achieves a 48-h average STH efficiency of 30%. These results demonstrate the potential of photovoltaic-electrolysis systems for cost-effective solar energy storage.

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Age-related osteoporosis is associated with the reduced capacity of bone marrow mesenchymal stem cells (BMSCs) to differentiate into osteoblasts instead of adipocytes. However, the molecular mechanisms that decide the fate of BMSCs remain unclear. In our study, microRNA-23a, and microRNA-23b (miR-23a/b) were found to be markedly downregulated in BMSCs of aged mice and humans. The overexpression of miR-23a/b in BMSCs promoted osteogenic differentiation, whereas the inhibition of miR-23a/b increased adipogenic differentiation. Transmembrane protein 64 (Tmem64), which has expression levels inversely related to those of miR-23a/b in aged and young mice, was identified as a major target of miR-23a/b during BMSC differentiation. In conclusion, our study suggests that miR-23a/b has a critical role in the regulation of mesenchymal lineage differentiation through the suppression of Tmem64.

RESUMO

Growth differentiation factor 11 (GDF11) is an important circulating factor that regulates aging. However, the role of GDF11 in bone metabolism remains unclear. The present study was undertaken to investigate the relationship between serum GDF11 level, bone mass, and bone turnover markers in postmenopausal Chinese women. Serum GDF11 level, bone turnover biochemical markers, and bone mineral density (BMD) were determined in 169 postmenopausal Chinese women (47-78 years old). GDF11 serum levels increased with aging. There were negative correlations between GDF11 and BMD at the various skeletal sites. After adjusting for age and body mass index (BMI), the correlations remained statistically significant. In the multiple linear stepwise regression analysis, age or years since menopause, BMI, GDF11, and estradiol were independent predictors of BMD. A significant negative correlation between GDF11 and bone alkaline phosphatase (BAP) was identified and remained significant after adjusting for age and BMI. No significant correlation was noted between cross-linked N-telopeptides of type I collagen (NTX) and GDF11. In conclusion, GDF11 is an independent negative predictor of BMD and correlates with a biomarker of bone formation, BAP, in postmenopausal Chinese women. GDF11 potentially exerts a negative effect on bone mass by regulating bone formation.

RESUMO

Polarization manipulation is essential in almost every photonic system ranging from telecommunications to bio-sensing to quantum information. This is traditionally achieved using bulk waveplates. With the developing trend of photonic systems towards integration and miniaturization, the need for an on-chip waveguide type waveplate becomes extremely urgent. However, this is very challenging using conventional dielectric waveguides, which usually require complex 3D geometries to alter the waveguide symmetry and are also difficult to create an arbitrary optical axis. Recently, a waveguide waveplate was realized using femtosecond laser writing, but the device length is in millimeter range. Here, for the first time we propose and experimentally demonstrate an ultracompact, on-chip waveplate using an asymmetric hybrid plasmonic waveguide to create an arbitrary optical axis. The device is only in several microns length and produced in a flexible integratable IC compatible format, thus opening up the potential for integration into a broad range of systems.

RESUMO

In this work, we demonstrate an improved method to simulate the characteristics of multijunction solar cell by introducing a bias-dependent luminescent coupling efficiency. The standard two-diode equivalent-circuit model with constant luminescent coupling efficiency has limited accuracy because it does not include the recombination current from photogenerated carriers. Therefore, we propose an alternative analytical method with bias-dependent luminescent coupling efficiency to model multijunction cell behavior. We show that there is a noticeable difference in the J-V characteristics and cell performance generated by simulations with a constant vs. bias-dependent coupling efficiency. The results indicate that introducing a bias-dependent coupling efficiency produces more accurate modeling of multijunction cell behavior under real operating conditions.

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Bone marrow mesenchymal stem cells (BMSCs) exhibit an age-dependent reduction in osteogenesis that is accompanied by an increased propensity toward adipocyte differentiation. This switch increases adipocyte numbers and decreases the number of osteoblasts, contributing to age-related bone loss. Here, we found that the level of microRNA-188 (miR-188) is markedly higher in BMSCs from aged compared with young mice and humans. Compared with control mice, animals lacking miR-188 showed a substantial reduction of age-associated bone loss and fat accumulation in bone marrow. Conversely, mice with transgenic overexpression of miR-188 in osterix+ osteoprogenitors had greater age-associated bone loss and fat accumulation in bone marrow relative to WT mice. Moreover, using an aptamer delivery system, we found that BMSC-specific overexpression of miR-188 in mice reduced bone formation and increased bone marrow fat accumulation. We identified histone deacetylase 9 (HDAC9) and RPTOR-independent companion of MTOR complex 2 (RICTOR) as the direct targets of miR-188. Notably, BMSC-specific inhibition of miR-188 by intra-bone marrow injection of aptamer-antagomiR-188 increased bone formation and decreased bone marrow fat accumulation in aged mice. Together, our results indicate that miR-188 is a key regulator of the age-related switch between osteogenesis and adipogenesis of BMSCs and may represent a potential therapeutic target for age-related bone loss.

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